Potassium chloride

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Feeding of male  F344 rats up to 5 % KCl in diet  ( approximatelyup to  1820 mg/kg bw/day) over a period of 2 years and feeding male and female Wistat rats with diets containing 3 %  KCl in diet  for up to 30 months did not affect the reproductive organs in the 2 strains of rats.

Additional information

There is no two generation reproductive toxicity study available.

However, in the available long term feeding studies with rats (see the respective section of repeated dose toxicity) no changes were reported in the absolute and relative organ weights of male and female reproductive organs and from histopatholpgical examinations no changes on reproductive organs were reported. Therefore , based on the available data, there is no reason to expect a specific reproductive toxicity of potassium chloride.

Furthermore, as confirmed by recent literature (Mangelsdorf 2003, Ulbrich & Palmer 1995, Janer et al 2007, Dent 2007, Sanbussisho 2009) rodents histopathological examinations of reproductive tissues in repeated dose studies are of high value and high sensitivity for the evaluation of reproductive toxicity in males and females. Histopathological changes on reproductive organs in repeated dose toxicity studies are indicative of effects on fertility. With this respect repeated-dose toxicity studies should be considered sensitive and sufficient information to evaluate toxicity on fertility if histological examination of the reproductive organs is covert.

Overall, based on the considerations above no further testing is required for the fertility assessment because potassium chloride has not shown specific effects on reproductive organs in male and female rats.

Furthermore UNEP, 2003, argued that based on the extensive amount of knowledge on KCl intake regulation and effects in the human body , further testing of fertility in not considered required under SIDS

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Mangelsdorf et al 2003: Some aspects relating to the evaluation of the effects of ch3emicals on male fertility. Regul. Toxicol. Pharmacol. 36, 69-98

Ulbrich & Palmer 1995: Detection of effects on male reproduction; a literature survey. J Am. College Toxicol 14, 293-327

Janer et al 2007: A retrospective analysis of the added value of the rat two generation reproductive toxicity study versus the rat subchronic toxicity study. Reprod. Toxicol 24, 103-113

Dent et al 2007: Strength and limitations of using repeated -dose toxicity studies to predict effects on fertility. Regul Toxicol. Pharmacol. 48, 241-258

Sanbussisho et al 2009: Collaborative work on evaluation of ovarian toxicity by repeated dose and fertility studies in female rats. J Tox Sci 34, Special Issue SP1-SP22

Short description of key information:
There is no two generation reproductive toxicity study available.
However, in the available long term feeding studies with rats (see the respective section of repeated dose toxicity) no effects on reproductive organs were reported Therefore , based on the available data, there is no reason to expect a specific reproductive toxicity of potassium chloride and no further testing is required for fertility assessment

Effects on developmental toxicity

Description of key information

In the available studies on developmental toxicity potassium chloride does not induce developmental toxicity and no maternal toxicity, neither in rats up to the highest test dose of 310 mg/kg bw  nor in mice up to 235 mg/kg bw.

Effect on developmental toxicity: via oral route

Dose descriptor:

NOAEL

310 mg/kg bw/day

Additional information

The two studies on developmental toxiciy available were not carried out under national or international guidelines and according to GLP. The robust summaries lack of necessary details because limited details are reported in the original publication. In the view of quality of the studies available and the well-documented mechanisms of action of KCl the information available is considered sufficient on this endpoint (UNEP 2003):

The administration of 2.35 up to 235 mg/kg bw of KCl to pregnant CD-1 mice for 10 consecutive days (gd 6 - gd 15, sacrifice already on gd17) had no clearly discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring sponateously in the sham-treated controls (FDRL 1975)

The administration of 3.1 up to 310.0 mg/kg bw of KCl to pregnant Wistar rats for 10 consecutive days (gd 6 - gd 15, sacrifice on gd 20) had no clearly discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring sponateously in the sham-treated controls (FDRL 1975)

Toxicity to reproduction: other studies

Additional information

Groups of male F344/Slc rats received 0, 0.25, 1, 5 % KCl in diet (corresponding to 0, 110, 450, 1820 mg/kg bw/day) over a period of 2 years and were observed for clinical signs and mortality and were examined for gross and histopathological changes at the end of the treatment period. No changes were reported in the absolute and relative organ weights of the testes, seminal vesicle and prostate or of histopathological changes of these organs (Imai 1961)

Male and female Wistar rats were fed diets containing 0 or 3 % KCL over a total period of 30 months: Examination after 13 weeks (10 rats/sex/group), after 18 months (15 rats/sex/group) and after 30 months (50 rats/sex /group). Due to the reduction of feed intake the mean test substance intake and mean body weight decreased in time. After 30 months treatment, reproductive organs on males and females were not affected by treatment. (Lina 1994, 2004)

Justification for classification or non-classification

Based on the available data no classification/labelling is proposed.